Asymmetric hydrogenation of dehydro-α-amino acid derivatives is a very widely used transformation in the pharmaceutical and fine chemicals industries. Rhodium catalysts containing chiral bisphosphine ligands provide ready access to these valuable synthetic targets with chiral purities routinely >95% ee, often with S/C ratios exceeding 104. For optimal hydrogenation performance, dehydro-amino acid substrates are typically protected as the enamide.
This invention relates to sulfonamide derived amino acid substrates for asymmetric hydrogenation utilizing rhodium, ruthenium and iridium metal catalysts. Processes for making N-sulfonamide α-amino acid derivatives from naturally occurring amino acids are disclosed in Cherney, Robert J. et al., J Med. Chem. (2003), 46(10), 1811-1823 and Inoue, Jun, et al., J. Med. Chem. (2003), 46(5), 868-871. Synthesis of N-sulfonamide amino acids via enzymatic methods is disclosed in Milne, H. Bayard, et al., J. Amer. Chem. Soc. (1957), 79, 645-648 and WO 2004/011449 (Wosikowski-Buters, Katja, et al.). See also U.S. Pat. No. 4,962,230, which discloses a process for making optically active carboxylic acids. See also U.S. Pat. No. 5,559,267.
More particularly, this invention relates to a process for preparing optically active α-amino acid derivatives which can be employed to make N-sulfonamide compounds that are useful against anthrax and/or for inhibiting lethal factor. This invention also relates to an efficient and scaleable synthesis for making lethal factor inhibitors for the treatment of anthrax infection. The N-sulfonamide compounds of this invention are disclosed in PCT patent application US03/16336 and U.S. patent application 60/530103, both herein incorporated by reference in their entirety.